| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the efficacy of Tec-Dara with DPd/DVd |
|
| E.2.2 | Secondary objectives of the trial |
- To further compare the efficacy of Tec-Dara with DPd/DVd
- To assess the safety profile of Tec-Dara
- To characterize the PK of teclistamab
- To assess the immunogenicity of teclistamab and daratumumab
- To compare the patient-reported outcomes (PROs) of Tec-Dara with DPd/DVd
- To evaluate the efficacy of teclistamab in-high-risk molecular subgroups
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. ≥18 years of age.
2. Criterion modified as per amendment 1.
2.1 Documented multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b. Measurable disease at screening as defined by any of the following:
1) Serum M-protein level ≥0.5 g/dL (central laboratory); or
2) Urine M-protein level ≥200 mg/24 hours (central laboratory); or
3) Serum immunoglobulin free light chain ≥10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Criterion modified as per amendment 1.
3.1 Received 1 to 3 prior line(s) of antimyeloma therapy (Appendix 6) including a PI and lenalidomide.
a. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory (ie, have demonstrated progressive disease by IMWG criteria during treatment or within 60 days of completion of lenalidomide-containing regimen). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion.
4. Documented evidence of progressive disease based on investigator’s determination of response by IMWG criteria on or after their last regimen.
5. Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment (Appendix 7).
6. Progression on or within 60 days of the last dose of lenalidomide given as maintenance
will meet this criterion.
6.1 Have clinical laboratory values meeting the criteria as defined in the protocol during the screening phase and also at start of administration of study treatment.
7. A woman of childbearing potential must have a negative highly-sensitive serum pregnancy test at screening and again within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study
8. Criterion modified as per amendment 1.
8.1. A woman must be:
a. Not of childbearing potential, or
b. Of childbearing potential and
1) Practicing true abstinence; or
2) Have a sole partner who is vasectomized; or
3) Practicing ≥1 highly-effective, user-independent method of contraception. For participants who are of childbearing potential and treated with DPd in Arm B, see Section 6.12.3 for details regarding concomitant use of estrogen-containing products and pomalidomide.
9. Criterion modified as per amendment 1.
9.1 A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 90 days after receiving the last dose of study treatment
10. Criterion modified as per amendment 1.
10.1 A man must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 90 days after receiving the last dose of study treatment. If a female partner is of childbearing potential, she must also be practicing a highly effective
method of contraception.
11. Criterion modified as per amendment 1.
11.1 A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study treatment.
12. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 5.3)
13. Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. |
|
| E.4 | Principal exclusion criteria |
1. Criterion modified as per amendment 1.
1.1 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator’s Brochure and appropriate package inserts), Additional exclusion criteria pertaining to specific study drugs include:
a. A participant is not eligible to receive DPd as control therapy if any of the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide (intolerance defined as prior therapy discontinued due to any AE related to pomalidomide)
2) Disease that is considered refractory to pomalidomide per IMWG (progression during treatment or within 60 days of completing treatment with pomalidomide).
b. A participant is not eligible to receive DVd as control therapy if any of the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib (intolerance defined as prior therapy discontinued due to any AE related to bortezomib)
2) Grade 1 peripheral neuropathy with pain or Grade ≥2 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
3) Disease that is considered refractory to bortezomib per IMWG (progression during treatment or within 60 days of completing treatment with bortezomib).
4) Received a strong CYP3A4 inducer (see Section 6.12.3.3) within 5 half-lives prior to randomization.
c. A participant is not eligible for this study if they are refractory to both pomalidomide and bortezomib.
2. Received any prior BCMA-directed therapy.
3. Has disease that is considered refractory to an anti-CD38 monoclonal antibody per IMWG (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody).
4. Received the following prior antimyeloma therapy, in the specified time frame prior to randomization:
a. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥5 half-lives, whichever is less
b. Investigational vaccine within 4 weeks
c. Monoclonal antibody therapy within 21 days
d. Cytotoxic therapy within 21 days
e. PI therapy within 14 days
f. IMiD agent therapy within 14 days
g. Radiotherapy within 14 days or focal radiation within 7 days
h. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months.
5. Stem cell transplant:
a. An allogeneic stem cell transplant within 6 months before randomization. Participants who received an allogeneic transplant must be off all immunosuppressive medications for ≥42 days without signs of graft-versus-host disease before randomization.
b. An autologous stem cell transplant within 12 weeks before randomization.
6. Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days before randomization.
7. Received a live, attenuated vaccine within 4 weeks before randomization.
8. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. The only allowed exceptions are:
a. Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured
b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
c. Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
d. Localized prostate cancer (N0M0):
1) With a Gleason score of ≤6, treated within the last 24 months, or untreated and under surveillance
2) With a Gleason score of 3+4 that has been treated >6 months prior to full study screening and considered to have a very low risk of recurrence, or
3) History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
e. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
f. Other malignancy that is considered cured with minimal risk of recurrence.
9. Plasma cell leukemia at the time of screening, Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis.
For a full list of exclusion criteria, please refer to section 5.2 of the study protocol
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Overall response (PR or better)
- VGPR or better
- CR or better
- MRD negativity
- PFS-2
- OS
- Time to next treatment |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 61 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Brazil |
| Canada |
| China |
| Japan |
| Korea, Republic of |
| Russian Federation |
| Taiwan |
| Ukraine |
| United States |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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